Evaluation of midazolam as an adjuvant to bupivacaine in supraclavicular brachial plexus block

Saad A Moharam; Ahmed S Basuoni; Ahmed A Abd-elhafez; Ahmed S Ibrahim

doi:10.4103/tmj.tmj_17_17

ORIGINAL ARTICLE

Year : 2017 | Volume : 45 | Issue : 2 | Page : 99-103

Evaluation of midazolam as an adjuvant to bupivacaine in supraclavicular brachial plexus block

Saad A Moharam MSc , Ahmed S Basuoni, Ahmed A Abd-elhafez, Ahmed S Ibrahim
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Tanta University, Tanta, Egypt

Date of Submission	21-Feb-2017
Date of Acceptance	09-May-2017
Date of Web Publication	13-Oct-2017

Correspondence Address:
Saad A Moharam
Department of Anesthesia and Surgical ICU Department, Faculty of Medicine, Tanta University, Ryad Ghorapa Street, El-Gharbya, Tanta, 31111, Albahr St, Tanta, 31512
Egypt

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/tmj.tmj_17_17

Abstract

Background
The duration of the supraclavicular brachial plexus block is limited by the duration of action of local anesthetic used for the block. Many adjuvants are used to prolong the duration of the block. Few studies were carried on evaluate the effects of using midazolam as an adjuvant to bupivacaine in supraclavicular brachial plexus block.
Aim
The aim of the study was to evaluate the anesthetic characteristics of adding midazolam to bupivacaine during ultrasound-guided supraclavicular brachial plexus block.
Patients and methods
The study was carried out on 96 patients scheduled for upper limb surgeries. They were divided into three equal groups to receive ultrasound-guided supraclavicular brachial plexus block using 30 ml bupivacaine 0.5% in group I, 30 ml bupivacaine 0.5% and 30 µg/kg midazolam in group II, and 30 ml bupivacaine 0.5% in addition to 30 µg/kg intravenous midazolam in group III.
Results
The onset of sensory and motor block were significantly faster, and the durations were significantly longer in group II compared with groups I and III; furthermore, postoperative analgesia was significantly prolonged in group II (P<0.05). Patients of group II had prolonged mild sedation compared with group III.
Conclusion
Midazolam is a valuable adjuvant to bupivacaine during ultrasound-guided supraclavicular brachial plexus block, which requires further evaluation.

Keywords: bupivacaine, midazolam, supraclavicular block

How to cite this article:
Moharam SA, Basuoni AS, Abd-elhafez AA, Ibrahim AS. Evaluation of midazolam as an adjuvant to bupivacaine in supraclavicular brachial plexus block. Tanta Med J 2017;45:99-103

How to cite this URL:
Moharam SA, Basuoni AS, Abd-elhafez AA, Ibrahim AS. Evaluation of midazolam as an adjuvant to bupivacaine in supraclavicular brachial plexus block. Tanta Med J [serial online] 2017 [cited 2023 May 31];45:99-103. Available from: http://www.tdj.eg.net/text.asp?2017/45/2/99/216687

Introduction

Supraclavicular brachial plexus block was first described by Kulenkampff [1]. It is a useful alternative to general anesthesia for upper limb surgery; moreover, it has a diagnostic and therapeutic importance in pain management [2]. Use of ultrasonography has resulted in an increase in success rate and decrease in complications of brachial plexus block [3],[4],[5].

Though bupivacaine, the most frequently used local anesthetic (LA) for brachial plexus block, has a favorable anesthetic properties, need for continuing improvement of quality of regional anesthesia and analgesia to fit with different types of surgeries directed the researchers to study several adjuvants, including midazolam, to fasten onset, prolong anesthetic and analgesic properties, and reduce total volume of bupivacaine used during regional anesthesia and analgesia techniques [6].

Midazolam is a short-acting water-soluble benzodiazepine. It is known to produce antinociception and potentiate the effects of LAs by its action on ionotropic γ-amino butyric acid-A receptors, stimulating influx of chloride ions and resulting in inhibition of nerve impulse conduction because of membrane hyperpolarization [7],[8]. However, there are few studies assessing the benefits and adverse effects of midazolam and bupivacaine during regional anesthesia and analgesia techniques.

Aim

The aim of this study was to evaluate the effects of adding midazolam to bupivacaine during ultrasound-guided supraclavicular brachial plexus block.

Patients and methods

This prospective, randomized, controlled observer-blinded study was carried out at the orthopedic and general surgery department at Tanta University Hospitals, Tanta, Egypt, during a period of 6 months (December 2014–June 2015). The study included 96 adult patients of both sex, ASA I–II, aged 18–65 years, and scheduled for upper limb surgery after obtaining approval from our institutional review board (no: 2703/08/14) and obtaining an informed written consent. Patients with previous history of allergy to LAs, local infection at the site of injection, coagulation disorders, and those with neurological or psychological deficit were excluded from the study.

The study participants were randomized using a computer-generated random numbers table into three equal groups (I, II, and III), with 32 patients each, to receive ultrasound-guided supraclavicular brachial plexus block using 30 ml plain bupivacaine 0.5% (Markyrene; Sigma-Aldrich, Gillingham, UK) in group I (control group), 30 ml plain bupivacaine 0.5% mixed with 30 µg/kg midazolam (Dormicum; Roche, Reinach, Switzerland) in group II, or 30 ml plain bupivacaine 0.5% in addition to intravenous midazolam 30 µg/kg in group III.

Preoperatively, patients were subjected to a careful history taking, complete physical examination, and routine laboratory investigations. LA mixtures were prepared in the operating room before patients’ arrival. Injectate was prepared in two 20 ml syringes, kept on a sterile table, and covered with a sterile drape. On arrival to the operating room, an intravenous line was established with 20 G cannula for giving intravenous maintenance fluids; monitoring of the heart rate and rhythm was done using three ECG electrodes placed over patient’s chest. Noninvasive arterial blood pressure cuff and pulse oximeter were attached to the noninvolved arm.

Patient was made to lay supine with a pillow under his shoulder to make the subclavian artery more prominent, head turned to opposite side, and ipsilateral arm kept beside him. Skin was disinfected using povidone iodine 10%, and the linear probe (6–12 MHz) of ultrasound machine (Sonoscape SSI-6000, Sonoscape Company Ltd, Shenzen, China) was placed firmly over supraclavicular fossa above the midpoint of clavicle. The probe was tilted caudally to obtain a cross-sectional view of the subclavian artery. The brachial plexus was seen as a collection of hypoechoic oval structures posterolateral and superficial to the artery as grape-like clusters around the artery. Lidocaine of 2 ml was injected in the skin 1 cm lateral to the probe. Needle for infiltration of LA (Visioplex; Vygon, Écouen, France) was advanced along long axis of the probe in the same plane of ultrasound beam. The needle was advanced from lateral to medial with constant visualization of the needle. First injection was given at the corner pocket bordered by the subclavian artery medially, first rib inferiorly, and trunks of the brachial plexus superolateral to the artery [9]. Then two injections superior and lateral to the subclavian artery were given.

The following parameters were recorded: patients’ characteristics (age, sex, weight, BMI, duration of surgery, ASA physical status and type of surgery); onset of sensory block (min) (time from end of LA injection till loss of pin brick sensation); onset of motor block (min) (time from end of LA injection till loss of motor power); duration of sensory block (h) (time from end of LA injection till return of pin brick sensation); duration of motor block (h) (time from end of LA injection till return of motor power); and duration of postoperative analgesia (h) (time from end of surgery till patient first rescue analgesia was asked). The degree of sedation was assessed before injection of LA (T₀), then at 15 min (T₁₅), 30 min (T₃₀), 45 min (T₄₅), 60 min (T₆₀), 90 min (T₉₀) after injection of LA and at the end of surgery (T_end). Patients were frequently examined for any complication as Horner’s syndrome, chest discomfort, voice changes, LA systemic toxicity, failed block, pneumothorax, and respiratory depression.

Pin brick sensation was assessed in areas supplied by terminal nerves of the brachial plexus, lateral side of forearm (musculocutaneous nerve), dorsum of hand over the second metacarpophalangeal joint (radial nerve), little finger (ulnar nerve), medial thenar eminence (median nerve), and medial side of the forearm (medial cutaneous nerve). Pin brick sensation in involved limb was compared with contralateral limb and graded according to a three-point scale [10]: 2=sharp pain (no sensory blockade), 1=reduced pain (incomplete sensory blockade), and 0=absent pain (complete sensory blockade).

Motor power was assessed by asking the patient to extend his elbow against resistance (radial nerve), flex his distal interphalangeal joint of the second finger (median nerve), abduct his middle and ring fingers (ulnar nerve), and flex his elbow against resistance (musculocutaneous nerve). Muscle power was compared in both sides, and graded in the involved limb on a three-grade scale [11]: 2=normal (no motor block), 1=reduced (incomplete motor block), and 0=unable to overcome gravity (complete motor block).

Block was considered successful if the terminal nerves of brachial plexus were completely anesthetized (pin brick sensation=0 and motor power=0). Pin brick sensation of grade 2 or 1, or motor power of grade 2 or 1 for more than 15 min was considered block failure that mandates administration of general anesthesia.

Degree of sedation was assessed according to Culebras and colleagues sedation score [12]: 0=awake and alert, 1=sleeping but easily arousable, 2=deep sleep, arousable, and 3=deep sleep, not arousable.

Statistical analysis was performed using Statistical Package for Social Studies, version 23 (IBM, Illinois, Chicago, USA). Data were presented as mean±SD, median, and n (%) when appropriate. The χ²-test was used for comparison of qualitative data and analysis of variance with post-hoc Tukey’s test when appropriate for quantitative data between the three groups. Data were considered significant when P value was below 0.05.

Results

Patients’ characteristics were comparable in the three groups with no statistically significant difference between the three groups (P>0.05) ([Table 1]).

Table 1 Patients, characteristics

Click here to view

Sensory and motor block onset times were significantly shorter in group II compared with other groups (P=0.001). Duration of sensory, motor block recovery time, and postoperative analgesia were significantly more prolonged in group II compared with groups I and III (P=0.001) ([Table 2]).

Table 2 Block characteristics

Click here to view

The sedation score in group I was 0 at all predetermined times. In group II the median value of sedation score was 0 after injection of LA mixture, and 1 at 15–60 min. Then, it returned to 0 at 90 min after block performance. Whereas in group III, the median value of sedation score was 0 after injection of LA and 1 at 15 min. Then, it returned to 0 at 30 min. Comparison of sedation scores in the three groups showed statistically significant higher score in group II at T_15–60 and group III at T₁₅ compared with group I at 15, 30, 45, and 60 min (P=0.001) ([Figure 1]).

Figure 1 Sedation score.

Click here to view

Horner’s syndrome occurred in 17 patients in all groups, with no statistically significant difference between the three groups (P=0.75). No other adverse events were detected ([Table 3]).

Table 3 Side effects occurred in the three groups

Click here to view

Discussion

The duration of the supraclavicular brachial plexus block is limited by the duration of action of LA used for the block. The present study showed that adding midazolam in a dose of 30 µg/kg to bupivacaine 0.5% in group II suggests a synergistic action of midazolam to bupivacaine on peripheral nerve trunks and excludes that these effects might be due to systemic absorption of midazolam as there was no difference in the anesthetic characteristics in group III. This was in agreement with the previous studies [13],[14],[15],[16],[17]. These studies used midazolam in a dose of 50 µg/kg mixed with different concentrations and volumes of LA; they suggested a synergistic action of midazolam to LA is responsible for the beneficial effects, and reported few respiratory complications with the 50 μg/kg dose of midazolam [13],[14],[15],[16],[17]. We obtained similar anesthetic characteristics without respiratory complications using a smaller dose of midazolam (30 µg/kg).

In contrast, Kim and colleagues studied 100 adult patients receiving supraclavicular brachial plexus anesthesia using lidocaine only (group I), midazolam added to lidocaine (group II), fentanyl added to lidocaine (group III), and midazolam and fentanyl added to lidocaine (group IV); they reported no statistically significant difference in the onset of sensory or motor blockades between the groups. It might be attributed to blind technique for supraclavicular brachial block that increased the incidence of LA injection away from the target nerves and thus more time was required for LA to diffuse and block the signal conduction in both sensory and motor fibers [18]. Ultrasound guidance allows the operator to manipulate the needle under direct vision to appropriate depth and place the needle tip immediately adjacent to the target nerve. A study done conducted by Williams and colleagues on 80 patients allocated into two equal groups to receive supraclavicular nerve block by ultrasound or nerve stimulator, using the same anesthetic mixture, reported that blocks performed by ultrasound guidance had more rapid onset than those with nerve stimulator. They reported fewer needle passes, less patient discomfort, and faster block performance time with no difference in success rates [13].

The present results showed that the onset of motor block was faster than the onset of sensory block in all groups, though it is well known that large motor fibers require longer time and higher concentration of LA than do small sensory fibers. This was in agreement with the observation of Dejong et al. [19]; LAs injected peripherally blocks motor fibers first because of the somatotopic arrangement of fibers in nerve bundle at the level of the trunks in which motor fibers are located more peripherally than are sensory fibers.

The patients of groups II and III showed mild sedation. It was of shorter duration in group III. Sedation is desirable during surgery and it could be due to partial vascular uptake of midazolam, and its effects on the central nervous system where it acts on γ-amino butyric acid receptors. The limited duration of sedation in case of intravenous midazolam (group III) could be explained by the fact that midazolam is highly lipophilic and has a short half life (1–2 h), whereas in group II, sedation was more prolonged than in group III due to slower absorption from perivascular neural tissues [20].

The incidence of Horner’s syndrome in the present study was similar to that in the previous reports [20],[21]. Horner’s syndrome results from paralysis of ipsilateral stellate ganglion due to spread of LA. Patients complained of mild anxiety, discomfort, and dissatisfaction, which required only reassurance [21]. None of our patients developed pneumothorax or accidental intravascular injection of LA, which was in agreement with the previous reports [22],[23]. Pneumothorax was reported in 6.1% of patients who received blind supraclavicular brachial plexus block [13], but ultrasound decreased the risks for intravascular injection and pneumothorax [13].

Safety of midazolam as an adjuvant to LAs during peripheral nerve block is still a challenge because of animal literature describing a range of histopathological neurotoxic changes occurring often with intrathecal midazolam [24]. However, in their study by Tucker et al. [25], conducted on 1100 patients, 547 patients received intrathecal midazolam (2 mg) added to bupivacaine, and 553 patients received bupivacaine alone. One week and 1 month after surgery, they found no neurologic symptoms in patients who received intrathecal midazolam.

Conclusion

From the previous results, we conclude that adding midazolam in a dose of 30 µg/kg to plain bupivacaine (0.5%) in supraclavicular brachial plexus block fastens the onset and prolongs the duration of both sensory and motor block, and postoperative analgesia. Moreover, it provides a favorably mild degree of sedation.

Further studies including a large number of patients are required for generalization of these results.

Acknowledgements

Authors’ contributions: All authors had equal role in design, work, statistical analysis and manuscript writing. All authors have approved the final article work.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Kulenkampf D. Anesthesia of the brachial plexus. Zentralbl Chir 1911; 38:1337–1350.
2.	Chan VW, Perlas A, McCartney CJ, Brull R, Xu D, Abbas S. Ultrasound-guided supraclavicular brachial plexus block. Anesth Analg 2003; 97:1514–1517.
3.	Sandhu NS, Capan LM. Ultrasound-guided infraclavicular brachial plexus block. Br J Anaesth 2002; 89:254–259.
4.	Jandard C, Gentili ME, Girard F, Ecoffey C, Heck M, Laxenaire MC et al. Infraclavicular block with lateral approach and nerve stimulation: extent of anesthesia and adverse effects. Reg Anesth Pain Med 2002; 27:37–42.
5.	Arcand G, Williams SR, Chouinard P, Harris P, Ruel M, Boudreault D et al. Ultrasound guided infraclavicular versus supraclavicular block. Anesth Analg 2005; 101:886–890.
6.	Culebras X, Van Gessel E, Hoffmeyer P, Gamulin Z. Clonidine combined with a long acting local anesthetic does not prolong postoperative analgesia after brachial plexus block but does induce hemodynamic changes. Anesth Analg 2001; 92:199–204.
7.	Olkkola KT, Ahonen J. Midazolam and other benzodiazepines. Handbook Exp Pharmacol. Springer-Verlag, Berlin, Germany. 2008; (III):335–360.
8.	Rudolph U, Crestani F, Benke D, Brünig I, Benson JA, Fritschy JM et al. Benzodiazepine actions mediated by specific gamma-amino butyric acid (A) receptor subtypes. Nature 1999; 40:796–800.
9.	Gupta A, Prakash S, Deshpande S, Kale KS. The effect of intrathecal midazolam 2.5 mg with hyperbaric bupivacaine on postoperative pain relief in patients undergoing orthopedic surgery. Internet J Anesthesiol 2007; 14:2.
10.	Soares LG, Brull R, Lai J, Chan VW. Eight ball, corner pocket: the optimal needle position for ultrasound-guided supraclavicular block. Reg Anesth Pain Med 2007; 32:94–95.
11.	Fredrickson MJ, Patel A, Young S, Chinchanwala S. Speed of onset of ‘corner pocket supraclavicular’ and infraclavicular ultrasound guided brachial plexus block: a randomised observer-blinded comparison. Amaesthesia 2009; 64:738–744.
12.	Chernik DA, Gillings D, Laine H, Silver J, Davidson A, Siegel J et al. Validity and reliability of the Observers’ Assessment of Alertness/Sedation scale: study with intrathecal midazolam. J Clin Psychopharmacol 1990; 10:244–251.
13.	Williams SR, Chouinard P, Arcand G, Harris P, Ruel M, Boudreault D et al. Ultrasound guidance speeds execution and improves the quality of supraclavicular block. Anesth Analg 2003; 97:1518–1523.
14.	Koj J, Yatindra KB, Nidhi BP. Brachial plexus block with midazolam and bupivacaine improves analgesia. Can J Anesth. 2005; 52:822–826.
15.	Laiq N, Khan MN, Arif M, Khan S. Midazolam with bupivacaine for improving analgesia quality in brachial plexus block for upper limb surgeries. J Coll Physicians Surg Pak 2008; 18:674–678.
16.	Shaikh SI, Veena K. Midazolam as an adjuvant in supraclavicular brachial plexus block. Anaesth Pain Intensive Care 2012; 16:7e11.
17.	Gautam SN, Bhatta SK, Sharma NR. A comparison on brachial plexus block using local anesthetic agents with and without midazolam. J Chitwan Med Coll 2013; 3:11e3.
18.	Kim MS, Hwang BS, Hwang BM, Kang SS, Son HJ, Cheong Y et al. The effect of the addition of fentanyl and midazolam to lidocaine in a supraclavicular brachial plexus block. Korean J Anesthesiol 2008; 54:167–172.
19.	Dejong RH, Wagman IH. Physiological mechanisms of peripheral nerve block by local anesthetics. Anesthesiology 1963; 24:684–727.
20.	Batwara D, Oza V, Nalwaya D, Vyas A, Parmar V. Efficacy of midazolam co-administered along with local anaesthetic solution in brachial plexus block. Int J Biomed Res 2014; 5:571–575.
21.	Borgeat A, Dullenkopf A, Ekatodramis G. Acute and non-acute complications associated with interscalene block. Anesthesiology 2001; 95:875–880.
22.	Gauss A, Tugtekin I, Georgieff M, Dinse‐Lambracht A, Keipke D, Gorsewski G. Incidence of clinically symptomatic pneumothorax in ultrasound‐guided infraclavicular and supraclavicular brachial plexus block. Anesthesia 2014; 69:327–336.
23.	Perlas A, Lobo G, Lo N, Brull R, Chan VW, Karkhanis R. Ultrasound guided supraclavicular block: outcome of 510 consecutive cases. Reg Anesth Pain Med 2009; 34:171–177.
24.	Hodgson PS, Neal JM, Pollock JE, Liu SS. The neurotoxicity of drugs given intrathecally. Anesth Analg 1999; 88:797–809.
25.	Tucker AP, Lai C, Nadeson R, Goodchild CS. Intrathecal midazolam I: a cohort study investigating safety. Anesth Analg 2004; 98:1512–1520.